HAIR-AN syndrome: a systematic review of clinical, metabolic, and hormonal features in women of reproductive age

Abstract Introduction: HAIR-AN syndrome (Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans) represents a distinct endocrinopathy characterized by severe insulin resistance (IR), hyperandrogenism, and cutaneous manifestations. It is frequently underdiagnosed and associated with significant metabolic and reproductive morbidity in women of reproductive age. Objective: This systematic review aimed to synthesize current evidence on the clinical, metabolic, and hormonal features of HAIR-AN syndrome among women of reproductive age, in order to characterize its phenotypic profile and therapeutic implications. Methods: A comprehensive literature search was conducted using PubMed, Embase, Scopus, and Web of Science databases up to June 2025. Eligible studies included observational and interventional designs reporting on women diagnosed with HAIR-AN syndrome. Data extraction focused on anthropometric, hormonal, and metabolic parameters. Risk of bias and methodological quality were assessed using the Newcastle-Ottawa Scale (NOS). Results: From an initial pool of 226 records, five studies met inclusion criteria. Findings indicate that HAIR-AN syndrome predominantly affects obese women, with marked IR (elevated HOMA-IR), hyperandrogenemia, and acanthosis nigricans severity correlating with metabolic dysfunction. Treatment strategies involving insulin-sensitizing agents, particularly incretin and metformin, demonstrated improvements in hormonal and metabolic profiles. Conclusion: HAIR-AN syndrome represents a unique and clinically relevant phenotype of severe IR with significant reproductive and dermatological manifestations. Early diagnosis and multidisciplinary management are essential to attenuate long-term metabolic complications.